Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

纸浆损失伴随着防御、感觉和营养供应的功能障碍。基于内源性干细胞的方法是一种潜在的牙髓再生策略。然而，内源性干细胞来源、外源性再生信号和新血管形成是基于内源性干细胞的牙髓再生的主要困难。因此，我们的研究目的是寻求一种有效的细胞因子传递策略和生物活性材料，为纸浆再生重建理想的再生微环境。在体外研究中，我们研究了 Wnt3a、转化生长因子-β 1 和骨形态发生蛋白 7 (BMP7) 对人牙髓干细胞 (h-DPSCs) 和人脐静脉内皮细胞的影响。基于胶原蛋白凝胶、基质胶的 2D 和 3D 培养系统，和明胶甲基丙烯酰被制造以评估 h-DPSCs 的形态和活力。在体内研究中，建立了异位裸鼠模型和原位比格犬模型，以研究通过植入载有BMP7的胶原凝胶进行牙髓再生的可能性。我们得出结论，BMP7 促进了 h-DPSCs 的迁移和牙源性分化以及血管形成。胶原凝胶在 2D 或 3D 培养中维持 h-DPSCs 的细胞粘附、细胞扩散和细胞活力。载有BMP7的胶原凝胶移植可在体内诱导血管化的牙髓样组织再生。基于胶原凝胶加载 BMP7 的注射方法可能在内源性牙髓再生中发挥有希望的治疗应用。建立异位裸鼠模型和原位比格犬模型，研究植入载有BMP7的胶原凝胶再生牙髓的可能性。我们得出结论，BMP7 促进了 h-DPSCs 的迁移和牙源性分化以及血管形成。胶原凝胶在 2D 或 3D 培养中维持 h-DPSCs 的细胞粘附、细胞扩散和细胞活力。载有BMP7的胶原凝胶移植可在体内诱导血管化的牙髓样组织再生。基于胶原凝胶加载 BMP7 的注射方法可能在内源性牙髓再生中发挥有希望的治疗应用。建立异位裸鼠模型和原位比格犬模型，研究植入载有BMP7的胶原凝胶再生牙髓的可能性。我们得出结论，BMP7 促进了 h-DPSCs 的迁移和牙源性分化以及血管形成。胶原凝胶在 2D 或 3D 培养中维持 h-DPSCs 的细胞粘附、细胞扩散和细胞活力。载有BMP7的胶原凝胶移植可在体内诱导血管化的牙髓样组织再生。基于胶原凝胶加载 BMP7 的注射方法可能在内源性牙髓再生中发挥有希望的治疗应用。我们得出结论，BMP7 促进了 h-DPSCs 的迁移和牙源性分化以及血管形成。胶原凝胶在 2D 或 3D 培养中维持 h-DPSCs 的细胞粘附、细胞扩散和细胞活力。载有BMP7的胶原凝胶移植可在体内诱导血管化的牙髓样组织再生。基于胶原凝胶加载 BMP7 的注射方法可能在内源性牙髓再生中发挥有希望的治疗应用。我们得出结论，BMP7 促进了 h-DPSCs 的迁移和牙源性分化以及血管形成。胶原凝胶在 2D 或 3D 培养中维持 h-DPSCs 的细胞粘附、细胞扩散和细胞活力。载有BMP7的胶原凝胶移植可在体内诱导血管化的牙髓样组织再生。基于胶原凝胶加载 BMP7 的注射方法可能在内源性牙髓再生中发挥有希望的治疗应用。